PROJECT SUMMARY Prenatal exposure to alcohol can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Despite increased education efforts urging pregnant women to not consume alcohol, estimates indicate that as much as 2% to 4% of all live births in the U.S. may be affected by prenatal alcohol exposure. Thus, FASD pose a serious public health problem. In addition, pregnant women who drink may also be consuming other illicit drugs. Cannabis is the most commonly used illicit drug among pregnant women, with overall prevalence rates ranging from 3% to 4%, and even higher rates in teen pregnancies. Furthermore, over half of pregnant women who are consuming cannabis are also consuming alcohol. Given the increase in availability of cannabis, combined with the increasing potency of ?9- tetrohydrocannabinol (THC), the principle psychoactive component of cannabis, prenatal exposure is likely to increase. However, the consequences of combined prenatal alcohol and cannabis exposure on brain and behavioral development are not well understood. Preclinical evidence indicates that THC increases alcohol- induced neurodegeneration, particularly during a model of late gestational exposure. In fact, alcohol's teratogenic effects can be attenuated by blocking CB1 receptors, suggesting that the cannabinoid receptors may mediate some of alcohol's effects on development. However, it is not clear how these interactions translate to behavioral alterations. Using an animal model, this proposal will examine the functional consequences of combined alcohol and THC. First, we will establish parameters of THC administration to model clinically relevant levels of THC exposure. Secondly, we will examine the effects of developmental exposure to alcohol, THC, and their combination on learning and memory, motor function, and emotional behaviors. These studies will lay a foundation so that future studies can strategically investigate the interaction of alcohol and cannabis on brain development, elucidate mechanisms of action, and determine if intervention effectiveness varies with co-exposure. Importantly, understanding the effects of prenatal exposure to both drugs has major implications, not only for the lives of affected individuals and families, but also for public health and establishing public policy.